Hypertension is one of representative lifestyle-related diseases. Hypertension which is left untreated for long time lays a heavy burden on the cardiovascular system and results in arteriosclerosis to progress, thus causing various disorders in important organs, such as cerebral hemorrhage, cerebral infarction, cardiac failure, angina pectoris, myocardial infarction, renal failure and the like. Accordingly, the purpose of treating hypertension lies not only in lowering the blood pressure, but also in improving and/or preventing disorders in important organs including brain, heart and kidney, by controlling the blood pressure. As a method of treating hypertension, there are available fundamental treatments based on improvement in the lifestyle, such as dietetic therapy, exercise therapy and the like, as well as an attempt to control the blood pressure by positive pharmaceutical intervention.
The renin-angiotensin (RA) system is a system of biosynthesis of angiotensin II (AII), which is a major vasopressor factor, and takes an important role in the control of the blood pressure and the amount of body fluid. AII exhibits a strong vasoconstrictive effect brought by the intervention of AII receptors on the cellular membrane, thus raising the blood pressure, and also promotes cellular propagation or production of extracellular matrix by directly acting on the AII receptors in the cardiac cells or renal cells. Therefore, drugs inhibiting increase in the activity of the RA system can be expected to have a blood pressure lowering action as well as a powerful organ protecting action, and thus active researches on such drugs have been conducted so far.
The method of inhibiting the AII action is broadly classified into methods of inhibiting the biosynthesis of AII and methods of inhibiting the binding of AII to AII receptors. For the drugs inhibiting the biosynthesis of AII, angiotensin converting enzyme (ACE) inhibitory drugs have been already put to practical use and are being confirmed to have a blood pressure lowering action as well as an effect for protecting various organs. However, since ACE is an enzyme identical to kininase II, which is a bradykinin degrading enzyme, ACE inhibitory drug inhibits the biosynthesis of AII as well as the degradation of bradykinin. As a result, ACE inhibitory drugs are believed to induce side effects such as dry cough, angioedema and the like, which are considered to be caused by accumulation of bradykinin.
As the drugs inhibiting the binding of AII to AII receptors, AII type 1 receptor blockers (ARB) have been developed. ARB has a merit in that it can inhibit, at the receptor level, the action of AII that is biosynthesized by not only ACE but also an enzyme other than ACE, such as chymase and the like. It is known that administration of ACE inhibitors and ARB increases the plasma renin activity (PRA) as a compensatory feedback effect, since these drugs act on a more peripheral region of the RA system.
Renin is an enzyme occupying a position at the uppermost stream of the RA system, and converts angiotensinogen to angiotensin I. A renin inhibitory drug inhibits the RA system by inhibiting the biosynthesis of AII in the same manner as the ACE inhibitory drugs do, and thus can be expected to have a blood pressure lowering action or an effect of protecting various organs. Since the renin inhibitory drug does not have influence on the metabolism of bradykinin, it is believed to have no risk of side effects such as dry cough and the like, that are observed with the ACE inhibitory drugs. Furthermore, while the ACE inhibitory drugs or ARB increase the PRA level, the renin inhibitory drugs are the only drugs that can reduce PRA.
As renin inhibitors, orally Administrable Aliskiren has been reported (Chem. Biol., 2000, vol. 7, pages 493-504; Hypertension, 2003, vol. 42, pages 1137-1143; J. Hypertens., 2005, vol. 23, pages 417-426 etc.).
Besides the above, the following compounds have been reported as renin inhibitors.    (1) A compound represented by the formula
    wherein R1 is hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocyclyl, or unsubstituted or substituted cycloalkyl;    R2 is unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted cycloalkyl, or acyl;    R3 is hydrogen, unsubstituted or substituted aryl, or unsubstituted or substituted alkyl;    R4 is unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted cycloalkyl, or acyl; or    R3 and R4 may form together a 3- to 7-membered nitrogen containing saturated hydrocarbon ring which can be unsubstituted or substituted;    R6 is hydrogen, halo, unsubstituted alkyl or unsubstituted alkoxy;    R7 and R8 are independently of each other hydrogen or halo; and    T is methylene or carbonyl, or a salt thereof (see WO2007/077005).    (2) A compound represented by the formula
    wherein R1 is hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocyclyl, or unsubstituted or substituted cycloalkyl;    R2 is unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted cycloalkyl, or acyl;    R3 is hydrogen, unsubstituted or substituted aryl, or unsubstituted or substituted alkyl;    R4 is unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted cycloalkyl, or acyl; or    R3 and R4 may form together a 3- to 7-membered nitrogen containing saturated hydrocarbon ring which can be unsubstituted or substituted; and    T is methylene or carbonyl, or a salt thereof (see WO2007/006534).    (3) A compound represented by the formula
    wherein R1a is a hydrogen atom, an optionally substituted C1-6 alkyl group or the like; R1b is a substituted C1-6 alkoxy group or the like; R1b is a hydrogen atom, an optionally substituted C1-6 alkoxy group or the like; R2 is a hydrogen atom, an optionally substituted C1-6 alkyl group or the like; R3a, R3b, R3c and R3d are the same or different and each independently is a group: -A-B (wherein A is a single bond, —(CH2)sO—, —(CH2)sN(R4)CO— etc., B is a hydrogen atom, an optionally substituted C1-6 alkyl group etc.) or the like; R4 is a hydrogen atom, an optionally substituted C1-6 alkyl group or the like; s is 0 or the like; n is 1 or the like, or a pharmacologically acceptable salt, for example, a compound of the following formula (see WO2008/093737).

On the other hand, as an amide compound, the following compounds have been reported.    (4) In EP711757, for example, a compound having the following formula has been reported as an α1-adrenergic receptor antagonist:
    (5) In U.S. Pat. No. 5,250,548, for example, a compound having the following formula has been reported as an AII receptor antagonist:
    (6) In Journal of Medicinal Chemistry, 1995, vol. 38, pages 1406-1410, a compound having the following formula has been reported as an intermediate for an HIV-1 reverse transcriptase inhibitor:
    (7) In WO01/83460, for example, compounds having the following formulas have been reported as compounds having a cGMP-specific phosphodiesterase (PDE) inhibitory action (PDE V inhibitory action):
    (8) In WO02/20489, for example, compounds having the following formulas have been reported as compounds having a PDE V inhibitory action:

However, these reports do not describe a renin inhibitory activity.
Other than the above, amide compounds having particular structures are disclosed as a cathepsin S inhibitor in WO2006/018284, as a kinase inhibitor in WO2004/080463, as a CNS disorder regulator in WO2007/047447, as a Na+—K+-2Cl− cotransporter antagonist in US2006/0089350, as a CCR5 antagonist in WO2004/054974, and as a glycine uptake inhibitor in WO2005/023260.    patent document 1: WO2007/077005    patent document 2: WO2007/006534    patent document 3: WO2008/093737    patent document 4: EP711757    patent document 5: U.S. Pat. No. 5,250,548    patent document 6: WO01/83460    patent document 7: WO02/20489    patent document 8: WO2006/018284    patent document 9: WO2004/080463    patent document 10: WO2007/047447    patent document 11: US2006/0089350    patent document 12: WO2004/054974    patent document 13: WO2005/023260    non-patent document 1: Journal of Medicinal Chemistry, 1995, vol. 38, pages 1406-1410